Tsutsui T, Suzuki N, Ohmori M
Cancer Res. 1984 Mar;44(3):938-41.
The effects of exposure of early-passage Syrian hamster embryo cells in culture to sodium fluoride have been studied with respect to induction of morphological and neoplastic transformation, chromosome aberrations, sister chromatid exchanges, and unscheduled DNA synthesis. Exposure of Syrian hamster embryo cells to NaF concentrations between 75 and 125 micrograms/ml for 24 hr caused approximately 90 to 40% cell survival and resulted in a dose-dependent increase in the frequency of morphological transformation of the cells. Mass cultures of cells treated with NaF (75 or 100 micrograms/ml) for 24 hr, followed by continuous cultivation for 35 to 50 passages, developed the ability to grow in soft agar and to produce anaplastic fibrosarcomas when injected into newborn hamsters. In contrast, no morphological and neoplastic transformation was observed in untreated cells. Furthermore, a significant increase in chromosome aberrations at the chromatid level, sister chromatid exchanges, and unscheduled DNA synthesis was induced by NaF in a dose- and time-dependent manner. These results indicate that NaF is genotoxic and capable of inducing neoplastic transformation of Syrian hamster embryo cells in culture. A potential for carcinogenicity of this chemical, which is widely used by humans, is suggested. However, the carcinogenic risk of this chemical to humans may be reduced by factors regulating in vivo dose levels.
研究了原代培养的叙利亚仓鼠胚胎细胞暴露于氟化钠后,在形态学和肿瘤转化诱导、染色体畸变、姐妹染色单体交换及DNA修复合成方面的影响。将叙利亚仓鼠胚胎细胞暴露于浓度为75至125微克/毫升的氟化钠中24小时,导致约90%至40%的细胞存活,并使细胞形态转化频率呈剂量依赖性增加。用氟化钠(75或100微克/毫升)处理24小时的细胞大量培养物,随后连续传代培养35至50代,获得了在软琼脂中生长的能力,并在注射到新生仓鼠体内时产生间变性纤维肉瘤。相比之下,未处理的细胞未观察到形态学和肿瘤转化。此外,氟化钠以剂量和时间依赖性方式诱导染色单体水平的染色体畸变、姐妹染色单体交换及DNA修复合成显著增加。这些结果表明,氟化钠具有遗传毒性,能够在培养中诱导叙利亚仓鼠胚胎细胞发生肿瘤转化。提示了这种被人类广泛使用的化学物质具有致癌潜力。然而,该化学物质对人类的致癌风险可能会因体内剂量水平调节因素而降低。